Abstract:
:Targeted toxin-based therapeutics are hindered by poor intracellular uptake, limited stability and non-specific immune stimulation. To address these problems, ligand-targeted toxins in combination with low dose saponin mixtures have been adapted and tested in vivo in the past, however, undefined saponin raw mixtures are not suitable for use in clinical development. In the present work we therefore used a targeted toxin (Sap3-EGF, i.e. saporin fused to epidermal growth factor) in combination with a structurally defined isolated saponin m/z 1861 (SO-1861). In vitro evaluation confirmed a 6900-fold enhancement in the cytotoxic efficacy of Sap3-EGF against TSA-EGFR target cells. The required dose of the targeted toxin was appreciably reduced and there was a highly synergistic effect observed. An ex vivo hemolysis assay showed no or very less hemolysis up to 10 μg/mL of SO-1861. In the acute toxicity studies SO-1861 was found to be non-toxic up to a dose of 100 μg/treatment. The enzymes aspartate aminotransferase, alanine aminotransferase, and glutamate dehydrogenase did not show any statistically significant liver damage, which was further confirmed by histological examination. Additionally, creatinine was also similar to the control group thus ruling out damage to kidney. In vivo studies in a syngeneic BALB/c tumor model characterized by EGFR overexpression were done by applying 30 μg SO-1861 and 0.1 μg Sap3-EGF per treatment. A more than 90% reduction (p < 0.05) in the average tumor volume was observed by this combined therapy.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Thakur M,Mergel K,Weng A,von Mallinckrodt B,Gilabert-Oriol R,Dürkop H,Melzig MF,Fuchs Hdoi
10.1016/j.molonc.2012.12.004subject
Has Abstractpub_date
2013-06-01 00:00:00pages
475-83issue
3eissn
1574-7891issn
1878-0261pii
S1574-7891(12)00130-5journal_volume
7pub_type
杂志文章abstract:PURPOSE:Lobular carcinoma in situ (LCIS) is both a risk indicator and non-obligate precursor of invasive lobular carcinoma (ILC). We sought to characterize the transcriptomic features of LCIS and ILC, with a focus on the identification of intrinsic molecular subtypes of LCIS and the changes involved in the progression ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.12.005
更新日期:2015-04-01 00:00:00
abstract::The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self-renewing cell populations that constitute the bulk of the tumor. Although, the CSC hypothesis does not directly address the cell of origin of cancer, it is...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2010.06.005
更新日期:2010-10-01 00:00:00
abstract::Glioblastoma (GBM) is an incurable brain tumor for which new treatment strategies are urgently needed. Next-generation sequencing of GBM has most often been performed retrospectively and on archival tissue from both diagnostic and relapse surgeries with limited knowledge of clinical information, including treatment gi...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12790
更新日期:2020-09-04 00:00:00
abstract::The main components of the cancer research continuum are basic/preclinical research, early and late clinical research and, after the adoption of an innovation by the healthcare or health organisations, outcomes research. Translational cancer research, defined as a coherent cancer research continuum, is mandatory to ad...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1002/1878-0261.12450
更新日期:2019-03-01 00:00:00
abstract::Angiogenin (ANG), a 14-kDa pro-angiogenic secreted protein, has been shown to play a role in cell migration and tumor invasion, which involve proteolytic cleavage of plasminogen to generate plasmin. However, the mechanism by which ANG regulates plasmin formation and cell migration was not known. Our studies here detec...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2013.12.017
更新日期:2014-05-01 00:00:00
abstract::JS-2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS-2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS-2 in a large cohort of patients with colorectal tumours and correlate these to the cl...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2011.06.003
更新日期:2011-10-01 00:00:00
abstract::Alterations in glycan structures are early signs of malignancy and have recently been proposed to be in part a driving force behind malignant transformation. Here, we explore whether differences in expression of genes related to the process of glycosylation exist between breast carcinoma subtypes - and look for their ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.12.013
更新日期:2015-04-01 00:00:00
abstract::It has been hypothesized based on accumulated data that a class of small noncoding RNAs, termed microRNAs, are key factors in intercellular communication. Here, microRNAs present in interstitial breast tumor fluids have been analyzed to identify relevant markers for a diagnosis of breast cancer and to elucidate the cr...
journal_title:Molecular oncology
pub_type: 临床试验,杂志文章
doi:10.1002/1878-0261.12025
更新日期:2017-02-01 00:00:00
abstract::As treatment options for patients with incurable metastatic castration-resistant prostate cancer (mCRPC) are considerably limited, novel effective therapeutic options are needed. Checkpoint kinase 1 (CHK1) is a highly conserved protein kinase implicated in the DNA damage response (DDR) pathway that prevents the accumu...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12756
更新日期:2020-10-01 00:00:00
abstract::cMet is a well-characterized oncogene that is the target of many drugs including small molecule and biologic pathway inhibitors, and, more recently, antibody-drug conjugates (ADCs). However, the clinical benefit from cMet-targeted therapy has been limited. We developed a novel cMet-targeted 'third-generation' ADC, TR1...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12600
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Breast cancer is a heterogeneous disease with different molecular subtypes that have varying responses to therapy. An ongoing challenge in breast cancer research is to distinguish high-risk patients from good prognosis patients. This is particularly difficult in the low-grade, ER-positive luminal A tumors, w...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.11.002
更新日期:2015-03-01 00:00:00
abstract::Gene and protein expression of programmed death-ligand 1 (PD-L1) are prognostic in early breast cancer (BC), but their prognostic information is inconsistent at least in some biological subgroups. The validated prognostic gene signatures (GS) in BC are mainly based on proliferation and estrogen receptor (ER)-related g...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12654
更新日期:2020-05-01 00:00:00
abstract::Vestibular schwannomas (VSs), the most common tumors of the cerebellopontine angle, arise from Schwann cells lining the vestibular nerve. Pharmacotherapies against VS are almost non-existent. Although the therapeutic inhibition of inflammatory modulators has been established for other neoplasms, it has not been explor...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.03.009
更新日期:2015-08-01 00:00:00
abstract::Cigarette smoking is one of the leading risks for lung cancer and is associated with the insensitivity of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, it remains undetermined whether and how cigarette smoke affects the therapeutic efficacy of...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12193
更新日期:2018-05-01 00:00:00
abstract::Molecular characterization of cancers is important in dictating prognostic factors and directing therapy. Next-generation sequencing of plasma circulating tumor DNA (ctDNA) offers less invasive, more convenient collection, and a more real-time representation of a tumor and its molecular heterogeneity than tissue. Howe...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12791
更新日期:2021-01-01 00:00:00
abstract::Bone morphogenetic proteins (BMPs) are a group of growth factors with dual functions in cancer development and progression. Recently, certain tumor-promoting roles have been identified for selected antagonists/inhibitors (BMPIs) of this developmental pathway. A recent focus on the implication of BMP in colorectal canc...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.04.004
更新日期:2014-10-01 00:00:00
abstract::Pancreatic cancer is one of the most lethal human cancers, and radiotherapy is often implemented for locally advanced pancreatic ductal adenocarcinoma. Tumor cell repopulation is a major challenge in treating cancers after radiotherapy. In order to address the problem of tumor repopulation, our previous studies have d...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.07.024
更新日期:2015-01-01 00:00:00
abstract::Lung metastasis is the major cause of death in osteosarcoma patients. However, molecular mechanisms underlying this metastasis remain poorly understood. To identify key molecules related with pulmonary metastasis of pediatric osteosarcomas, we analyzed high-throughput miRNA expression in a cohort of 11 primary tumors ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.04.004
更新日期:2016-08-01 00:00:00
abstract::Transient receptor potential melastatin-4 channel (TRPM4) dysregulation contributes to heart conditions, immune diseases, and cervical and prostate cancer. Up to now, the involvement of TRPM4 in colorectal cancer (CRC) pathophysiology remains unknown. Here, we investigated tumor tissue microarrays from 379 CRC patient...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12566
更新日期:2019-11-01 00:00:00
abstract::The PI3K/Akt signaling pathway, the most frequently altered signaling system in human cancer, is a crucial inducer of dysregulated proliferation and neoplastic processes; however, few therapeutic strategies using PI3K/Akt inhibitors singly have been shown to be effective. The purpose of this paper was to underline the...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12888
更新日期:2020-12-18 00:00:00
abstract::Around 50% of all human microRNAs reside within introns of coding genes and are usually co-transcribed. Gene expression datasets, therefore, should contain a wealth of miRNA-relevant latent information, exploitable for many basic and translational research aims. The present study was undertaken to investigate this pos...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.10.001
更新日期:2015-02-01 00:00:00
abstract::Histone deacetylases (HDACs), originally described as histone modifiers, have more recently been demonstrated to target a variety of other proteins unrelated to the chromatin environment. In this context, our present work demonstrates that the pharmacological or genetic abrogation of HDAC6 in primary melanoma samples ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.12.012
更新日期:2016-05-01 00:00:00
abstract::Cancer is a multifactorial and heterogeneous disease. The corresponding complexity appears at multiple levels: from the molecular and the cellular constitution to the macroscopic phenotype, and at the diagnostic and therapeutic management stages. The overall complexity can be approximated to a certain extent, e.g. cha...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2014.08.013
更新日期:2015-01-01 00:00:00
abstract::Brain metastases are life-threatening complications of triple-negative breast cancer, melanoma, and a few other tumor types. Poor outcome of cerebral secondary tumors largely depends on the microenvironment formed by cells of the neurovascular unit, among which pericytes are the least characterized. By using in vivo a...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12752
更新日期:2020-09-01 00:00:00
abstract::Autophagy, a well-described cellular mechanism for lysosomal degradation of cytoplasmic content, has emerged as a tumour suppression pathway. Recent evidence indicates that the tumour suppressor function of autophagy is mediated by scavenging of damaged oxidative organelles, thereby preventing accumulation of toxic ox...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2009.05.007
更新日期:2009-08-01 00:00:00
abstract::Deregulation of microRNAs contributes to the aberrant growth of hepatocellular carcinoma (HCC). Here, we showed that miR-634 expression was frequently decreased in HCC. Low miR-634 expression was significantly associated with larger tumor size, poorer tumor differentiation, advanced TNM stage, vascular invasion, absen...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.09.001
更新日期:2016-12-01 00:00:00
abstract::Triple-negative breast cancer (TNBC), the most refractory subtype of breast cancer to current treatments, accounts disproportionately for the majority of breast cancer-related deaths. This is largely due to cancer plasticity and the development of cancer stem cells (CSCs). Recently, distinct yet interconvertible mesen...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12167
更新日期:2018-04-01 00:00:00
abstract::The above article, published online on 28 February 2020 in Wiley Online Library (wileyonlinelibrary.com) as an Accepted Article (https://doi.org/10.1002/1878-0261.12656), has been withdrawn at the authors' request, and in agreement between the authors, the journal Editors in Chief J. E. Celis and K. Ryan, and John Wil...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12656
更新日期:2020-12-01 00:00:00
abstract::In order to secure high-quality cancer care for increasing numbers of cancer patients in the upcoming decades, the complete continuum of cancer research and cancer care needs a thorough overhaul, with more emphasis on prevention and early detection, and a greater focus on the development of innovative treatments that ...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1002/1878-0261.12441
更新日期:2019-03-01 00:00:00
abstract::Our limited understanding of the biological impact of the whole spectrum of early breast lesions together with a lack of accurate molecular-based risk criteria for the diagnosis and assignment of prognostic significance to biopsy findings presents an important problem in the clinical management of patients harboring p...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2010.09.005
更新日期:2010-12-01 00:00:00